Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Bacteremias and invasive fungal diseases in children receiving etanercept for steroid-resistant acute GVHD

Bone Marrow Transplantation volume 46, pages 159–160 (2011)Cite this article

Subjects

GVHD is the main complication occurring after allo-SCT and steroids are the first-line therapy for acute GVHD (aGVHD), with a 35% complete response rate.1 Use of monoclonal antibodies against TNF-α is one of the possible therapeutic approaches for steroid-refractory cases and recent studies in adults have shown that etanercept is effective.1, 2, 3 However, large studies in patients treated with anti-TNF-α for severe autoimmune diseases showed that infections, especially tuberculosis, invasive mycoses and bacteremias, are important complications, even if patients receiving etanercept show the lowest incidence of these severe adverse events.4, 5 Data in adults treated with etanercept for steroid-refractory aGVHD indicated an incidence of complicating bacterial and fungal infections ranging from 14 to 80%.2, 6, 7 Currently, there are no studies available on the occurrence of severe infections in children receiving etanercept for steroid-refractory aGVHD.

In September 2007, we started a program of etanercept administration for treating steroid-refractory aGVHD in children receiving allogeneic SCT at G Gaslini Children's Hospital, Genova,Italy. Etanercept was administered s.c. twice weekly for 8 weeks (16 doses) at a dose of 0.4 mg/kg (maximum dose, 25 mg). During etanercept treatment, methylprednisolone was maintained at a dose of 2 mg/kg/day for at least 1 week after the initial response to therapy and the dose was then tapered as appropriate. The protocol was approved by the Hospital Ethics Committee. All parents signed the informed consent as per the Declaration of Helsinki. The presence of an uncontrolled infection or personal or familial history of tuberculosis was an exclusion criterion. The management protocol for infectious complications following SCT included (1) fluconazole prophylaxis until day +100 from SCT; (2) low dosage of trimethoprim-sulfamethoxazole for Pneumocystis jirovecii prophylaxis; and (3) high dosage of acyclovir for Herpes simplex virus, VZV and CMV prophylaxis. In case of febrile complications, blood cultures were performed and empirical antibacterial therapy was started; sequential evaluation of galactomannan and computed tomography (CT) scans were performed for early detection of invasive fungal diseases (IFDs), and cultures for bacteria and fungi were performed at any suspected site of infection. The incidence of infectious complications was one of the variables that had to be monitored to evaluate the safety of the experimental program.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Levine JE, Paczesny S, Mineishi S, Braun T, Choi SW, Hutchinson RJ et al. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood 2008; 111: 2470–2475.

    Article  CAS  Google Scholar 

  2. Alousi AM, Weisdorf DJ, Logan BR, Bolanos-Meade J, Carter S, Difronzo N et al. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the blood and marrow transplant clinical trials network. Blood 2009; 114: 511–517.

    Article  CAS  Google Scholar 

  3. Ferrara JL . Advances in the clinical management of GVHD. Best Pract Res Clin Haematol 2008; 21: 677–682.

    Article  CAS  Google Scholar 

  4. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V . Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 2006; 295: 2275–2285.

    Article  CAS  Google Scholar 

  5. Tsiodras S, Samonis G, Boumpas DT, Kontoyiannis DP . Fungal infections complicating tumor necrosis factor alpha blockade therapy. Mayo Clin Proc 2008; 83: 181–194.

    Article  CAS  Google Scholar 

  6. Busca A, Locatelli F, Marmont F, Ceretto C, Falda M . Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol 2007; 82: 45–52.

    Article  CAS  Google Scholar 

  7. Weisdorf D, Haake R, Blazar B, Miller W, McGlave P, Ramsay N et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood 1990; 75: 1024–1030.

    CAS  PubMed  Google Scholar 

  8. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813–1821.

    Article  Google Scholar 

  9. Castagnola E, Bagnasco F, Faraci M, Caviglia I, Caruso S, Cappelli B et al. Incidence of bacteremias and invasive mycoses in children undergoing allogeneic hematopoietic stem cell transplantation: a single center experience. Bone Marrow Transplant 2008; 41: 339–347.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Haematology-Oncology Department, HSCT Unit, G Gaslini Children's Research Institute, Genova, Italy

    M Faraci, E Lanino, G Morreale, S Giardino & M Fossati

  2. Haematology-Oncology Department, Infectious Diseases Unit, G Gaslini Children's Research Institute, Genova, Italy

    C Moroni, I Caviglia & E Castagnola

Authors
  1. M Faraci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Lanino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Morreale
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Giardino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Fossati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Moroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I Caviglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E Castagnola
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Faraci.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faraci, M., Lanino, E., Morreale, G. et al. Bacteremias and invasive fungal diseases in children receiving etanercept for steroid-resistant acute GVHD. Bone Marrow Transplant 46, 159–160 (2011). https://doi.org/10.1038/bmt.2010.80

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.80

This article is cited by

Search

Advanced search

Quick links